Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Marta Espinosa, Juan Maria Roldán-Romero, Ignacio Duran, Enrique de Álava, María Apellaniz-Ruiz, Alberto Cascón, Carmen Garrigos, Mercedes Robledo, Cristina Rodriguez-Antona

ABSTRACT

BACKGROUND: Renal epithelioid angiomyolipomas (EAML) are rare tumors with aggressive behavior. EAML can be sporadic or develop within the tuberous sclerosis complex syndrome, where mutations of TSC1 or TSC2 genes (critical negative regulators of mTOR Complex 1) result in an increased activation of mTOR pathway. Optimal EAML treatment, including mTOR inhibitors, remains undetermined. CASE PRESENTATION: Here we present the case of a young adult with a renal EAML that after radical nephrectomy developed metastases, first in liver and then in lumbar vertebrae. After complete surgical resection of these lesions, liver recurrence was detected, this time with incomplete surgical resection. After finding a new liver lesion, systemic treatment with sirolimus started. The patient exhibited a complete and durable response to this drug, being disease free at the time of publication, after 36 months of treatment. Targeted next generation sequencing (NGS) of MTOR, TSC1 and TSC2 genes in the primary tumor, metastasis and blood of the patient, revealed one inactivating TSC2 mutation (c.2739dup; p.K914*) in the tumor cells. Immunohistochemistry revealed decreased TSC2 protein content and increased phospho-S6 in the tumor cells, demonstrating mTOR pathway activation. CONCLUSION: NGS on an EAML patient with an extraordinary response to sirolimus uncovered TSC2 inactivation as the mechanism for the response. This study supports NGS as a useful tool to identify patients sensitive to mTOR inhibitors and supports the treatment of malignant EAML with these drugs. More... »

PAGES

561

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12885-018-4467-6

DOI

http://dx.doi.org/10.1186/s12885-018-4467-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1104000104

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29764404


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Hospital Universitario Virgen del Roc\u00edo", 
          "id": "https://www.grid.ac/institutes/grid.411109.c", 
          "name": [
            "Medical Oncology Department, Hospital Virgen del Roc\u00edo, Servicio de Oncolog\u00eda Medica, Avenida Manuel Siurot s/n, 41013, Sevilla, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Espinosa", 
        "givenName": "Marta", 
        "id": "sg:person.014362730421.86", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014362730421.86"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Spanish National Cancer Research Centre", 
          "id": "https://www.grid.ac/institutes/grid.7719.8", 
          "name": [
            "Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fern\u00e1ndez Almagro 3, 28029, Madrid, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rold\u00e1n-Romero", 
        "givenName": "Juan Maria", 
        "id": "sg:person.015155427767.68", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015155427767.68"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Biomedicine of Seville", 
          "id": "https://www.grid.ac/institutes/grid.414816.e", 
          "name": [
            "Medical Oncology Department, Hospital Virgen del Roc\u00edo, Servicio de Oncolog\u00eda Medica, Avenida Manuel Siurot s/n, 41013, Sevilla, Spain", 
            "Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Roc\u00edo/CSIC/Universidad de Sevilla, Sevilla, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Duran", 
        "givenName": "Ignacio", 
        "id": "sg:person.01044677633.24", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01044677633.24"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Biomedicine of Seville", 
          "id": "https://www.grid.ac/institutes/grid.414816.e", 
          "name": [
            "Pathology Department, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Roc\u00edo/CSIC/Universidad de Sevilla-CIBERONC, Sevilla, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "de \u00c1lava", 
        "givenName": "Enrique", 
        "id": "sg:person.01325400051.79", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01325400051.79"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Spanish National Cancer Research Centre", 
          "id": "https://www.grid.ac/institutes/grid.7719.8", 
          "name": [
            "Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fern\u00e1ndez Almagro 3, 28029, Madrid, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Apellaniz-Ruiz", 
        "givenName": "Mar\u00eda", 
        "id": "sg:person.01265544650.31", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01265544650.31"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Centre for Biomedical Network Research on Rare Diseases", 
          "id": "https://www.grid.ac/institutes/grid.452372.5", 
          "name": [
            "Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fern\u00e1ndez Almagro 3, 28029, Madrid, Spain", 
            "Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Valencia, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Casc\u00f3n", 
        "givenName": "Alberto", 
        "id": "sg:person.0665541011.60", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0665541011.60"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Biomedicine of Seville", 
          "id": "https://www.grid.ac/institutes/grid.414816.e", 
          "name": [
            "Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Roc\u00edo/CSIC/Universidad de Sevilla, Sevilla, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Garrigos", 
        "givenName": "Carmen", 
        "id": "sg:person.01244725741.43", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01244725741.43"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Centre for Biomedical Network Research on Rare Diseases", 
          "id": "https://www.grid.ac/institutes/grid.452372.5", 
          "name": [
            "Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fern\u00e1ndez Almagro 3, 28029, Madrid, Spain", 
            "Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Valencia, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Robledo", 
        "givenName": "Mercedes", 
        "id": "sg:person.0716606465.40", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0716606465.40"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Centre for Biomedical Network Research on Rare Diseases", 
          "id": "https://www.grid.ac/institutes/grid.452372.5", 
          "name": [
            "Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fern\u00e1ndez Almagro 3, 28029, Madrid, Spain", 
            "Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Valencia, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rodriguez-Antona", 
        "givenName": "Cristina", 
        "id": "sg:person.0755677367.02", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755677367.02"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1126/science.1226344", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001422456"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/modpathol.2013.72", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007491127", 
          "https://doi.org/10.1038/modpathol.2013.72"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/2159-8290.cd-13-0353", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010294909"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/ijc.27800", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010380505"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pas.0b013e3181d90370", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010591966"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pas.0b013e3181d90370", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010591966"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pas.0b013e3181d90370", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010591966"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pas.0b013e3181d90370", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010591966"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/path.2289", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010793228"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pgen.1006242", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017142251"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2559.2009.03420.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018030987"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1365-2559.2009.03420.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018030987"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1469-1809.2003.00012.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019494306"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2009.26.3061", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021365418"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1477-7819-10-181", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023300116", 
          "https://doi.org/10.1186/1477-7819-10-181"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/iju.12116", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025276639"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2009.25.2981", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027949240"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0024919", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028361423"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jjco/hyr035", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029699939"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pas.0b013e318206f2a9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030285373"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/pas.0b013e318206f2a9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030285373"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2169/internalmedicine.48.2411", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035077670"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2169/internalmedicine.48.2411", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035077670"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3892/ol.2015.3846", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035118820"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3892/ol.2015.3846", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035118820"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1464-410x.2012.11618.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035537607"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/gcc.2870130411", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038005025"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4081/rt.2013.e46", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039826284"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4081/rt.2013.e46", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039826284"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0158476", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042334411"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.humpath.2007.01.028", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044406433"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00261-014-0129-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047240020", 
          "https://doi.org/10.1007/s00261-014-0129-6"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0140-6736(12)61767-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047847005"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1056/nejmoa1403352", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050082768"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/iju.12095", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053259561"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-15-2631", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063225221"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-15-2631", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1063225221"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.5489/cuaj.2823", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1072920617"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1159/000475142", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1082489447"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2017.03.035", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084524353"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-12", 
    "datePublishedReg": "2018-12-01", 
    "description": "BACKGROUND: Renal epithelioid angiomyolipomas (EAML) are rare tumors with aggressive behavior. EAML can be sporadic or develop within the tuberous sclerosis complex syndrome, where mutations of TSC1 or TSC2 genes (critical negative regulators of mTOR Complex 1) result in an increased activation of mTOR pathway. Optimal EAML treatment, including mTOR inhibitors, remains undetermined.\nCASE PRESENTATION: Here we present the case of a young adult with a renal EAML that after radical nephrectomy developed metastases, first in liver and then in lumbar vertebrae. After complete surgical resection of these lesions, liver recurrence was detected, this time with incomplete surgical resection. After finding a new liver lesion, systemic treatment with sirolimus started. The patient exhibited a complete and durable response to this drug, being disease free at the time of publication, after 36\u00a0months of treatment. Targeted next generation sequencing (NGS) of MTOR, TSC1 and TSC2 genes in the primary tumor, metastasis and blood of the patient, revealed one inactivating TSC2 mutation (c.2739dup; p.K914*) in the tumor cells. Immunohistochemistry revealed decreased TSC2 protein content and increased phospho-S6 in the tumor cells, demonstrating mTOR pathway activation.\nCONCLUSION: NGS on an EAML patient with an extraordinary response to sirolimus uncovered TSC2 inactivation as the mechanism for the response. This study supports NGS as a useful tool to identify patients sensitive to mTOR inhibitors and supports the treatment of malignant EAML with these drugs.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1186/s12885-018-4467-6", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1024632", 
        "issn": [
          "1471-2407"
        ], 
        "name": "BMC Cancer", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "18"
      }
    ], 
    "name": "Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation", 
    "pagination": "561", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "de823dfd7789040fbe3163a684b0500f545ba9dcc5d85940e0e6c6adab0160a0"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29764404"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "100967800"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s12885-018-4467-6"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1104000104"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s12885-018-4467-6", 
      "https://app.dimensions.ai/details/publication/pub.1104000104"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T14:19", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8660_00000572.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1186%2Fs12885-018-4467-6"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s12885-018-4467-6'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12885-018-4467-6'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12885-018-4467-6'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12885-018-4467-6'


 

This table displays all metadata directly associated to this object as RDF triples.

232 TRIPLES      21 PREDICATES      60 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s12885-018-4467-6 schema:about anzsrc-for:11
2 anzsrc-for:1112
3 schema:author Ne9c1dd0a1d4c41d5b9d116879f97577c
4 schema:citation sg:pub.10.1007/s00261-014-0129-6
5 sg:pub.10.1038/modpathol.2013.72
6 sg:pub.10.1186/1477-7819-10-181
7 https://doi.org/10.1002/gcc.2870130411
8 https://doi.org/10.1002/ijc.27800
9 https://doi.org/10.1002/path.2289
10 https://doi.org/10.1016/j.cell.2017.03.035
11 https://doi.org/10.1016/j.humpath.2007.01.028
12 https://doi.org/10.1016/s0140-6736(12)61767-x
13 https://doi.org/10.1046/j.1469-1809.2003.00012.x
14 https://doi.org/10.1056/nejmoa1403352
15 https://doi.org/10.1093/jjco/hyr035
16 https://doi.org/10.1097/pas.0b013e3181d90370
17 https://doi.org/10.1097/pas.0b013e318206f2a9
18 https://doi.org/10.1111/iju.12095
19 https://doi.org/10.1111/iju.12116
20 https://doi.org/10.1111/j.1365-2559.2009.03420.x
21 https://doi.org/10.1111/j.1464-410x.2012.11618.x
22 https://doi.org/10.1126/science.1226344
23 https://doi.org/10.1158/1078-0432.ccr-15-2631
24 https://doi.org/10.1158/2159-8290.cd-13-0353
25 https://doi.org/10.1159/000475142
26 https://doi.org/10.1200/jco.2009.25.2981
27 https://doi.org/10.1200/jco.2009.26.3061
28 https://doi.org/10.1371/journal.pgen.1006242
29 https://doi.org/10.1371/journal.pone.0024919
30 https://doi.org/10.1371/journal.pone.0158476
31 https://doi.org/10.2169/internalmedicine.48.2411
32 https://doi.org/10.3892/ol.2015.3846
33 https://doi.org/10.4081/rt.2013.e46
34 https://doi.org/10.5489/cuaj.2823
35 schema:datePublished 2018-12
36 schema:datePublishedReg 2018-12-01
37 schema:description BACKGROUND: Renal epithelioid angiomyolipomas (EAML) are rare tumors with aggressive behavior. EAML can be sporadic or develop within the tuberous sclerosis complex syndrome, where mutations of TSC1 or TSC2 genes (critical negative regulators of mTOR Complex 1) result in an increased activation of mTOR pathway. Optimal EAML treatment, including mTOR inhibitors, remains undetermined. CASE PRESENTATION: Here we present the case of a young adult with a renal EAML that after radical nephrectomy developed metastases, first in liver and then in lumbar vertebrae. After complete surgical resection of these lesions, liver recurrence was detected, this time with incomplete surgical resection. After finding a new liver lesion, systemic treatment with sirolimus started. The patient exhibited a complete and durable response to this drug, being disease free at the time of publication, after 36 months of treatment. Targeted next generation sequencing (NGS) of MTOR, TSC1 and TSC2 genes in the primary tumor, metastasis and blood of the patient, revealed one inactivating TSC2 mutation (c.2739dup; p.K914*) in the tumor cells. Immunohistochemistry revealed decreased TSC2 protein content and increased phospho-S6 in the tumor cells, demonstrating mTOR pathway activation. CONCLUSION: NGS on an EAML patient with an extraordinary response to sirolimus uncovered TSC2 inactivation as the mechanism for the response. This study supports NGS as a useful tool to identify patients sensitive to mTOR inhibitors and supports the treatment of malignant EAML with these drugs.
38 schema:genre research_article
39 schema:inLanguage en
40 schema:isAccessibleForFree true
41 schema:isPartOf N904210a9bbee43b099dadb53756fcad3
42 Nbe02a3aed08a4521b0a0b53e07004dfd
43 sg:journal.1024632
44 schema:name Advanced sporadic renal epithelioid angiomyolipoma: case report of an extraordinary response to sirolimus linked to TSC2 mutation
45 schema:pagination 561
46 schema:productId N08f530d0e23b4e45a17ab0f8beb50234
47 N42965620dd044269ae66f6eb49d88e7f
48 Nd00978cfb14943929407f6f22a63c485
49 Ne965d9af355a4500a68b397041f52b62
50 Nff9569e6f28a40cd99d67e5de320897c
51 schema:sameAs https://app.dimensions.ai/details/publication/pub.1104000104
52 https://doi.org/10.1186/s12885-018-4467-6
53 schema:sdDatePublished 2019-04-10T14:19
54 schema:sdLicense https://scigraph.springernature.com/explorer/license/
55 schema:sdPublisher N63986a4e4d6f4b4088b732ba8e47275e
56 schema:url https://link.springer.com/10.1186%2Fs12885-018-4467-6
57 sgo:license sg:explorer/license/
58 sgo:sdDataset articles
59 rdf:type schema:ScholarlyArticle
60 N05687dc225d34c199f2b83d0452534d1 rdf:first sg:person.01325400051.79
61 rdf:rest N0ead8d38501a4553aff87ff551b9d5b0
62 N08f530d0e23b4e45a17ab0f8beb50234 schema:name nlm_unique_id
63 schema:value 100967800
64 rdf:type schema:PropertyValue
65 N0ead8d38501a4553aff87ff551b9d5b0 rdf:first sg:person.01265544650.31
66 rdf:rest N5d3c7f64da7b4b55ae1589d582c15057
67 N2cdfea5877a24e09982f0872289a328b rdf:first sg:person.0716606465.40
68 rdf:rest N964501357fea42b396a01dad2c4ccd21
69 N42965620dd044269ae66f6eb49d88e7f schema:name dimensions_id
70 schema:value pub.1104000104
71 rdf:type schema:PropertyValue
72 N4abb349852ce44e08a5478a5ef3046c1 rdf:first sg:person.015155427767.68
73 rdf:rest N500833da7f024554a646f9ec6a92fc69
74 N500833da7f024554a646f9ec6a92fc69 rdf:first sg:person.01044677633.24
75 rdf:rest N05687dc225d34c199f2b83d0452534d1
76 N5d3c7f64da7b4b55ae1589d582c15057 rdf:first sg:person.0665541011.60
77 rdf:rest Nbc98c6563c55493b977b08eb8332236f
78 N63986a4e4d6f4b4088b732ba8e47275e schema:name Springer Nature - SN SciGraph project
79 rdf:type schema:Organization
80 N904210a9bbee43b099dadb53756fcad3 schema:volumeNumber 18
81 rdf:type schema:PublicationVolume
82 N964501357fea42b396a01dad2c4ccd21 rdf:first sg:person.0755677367.02
83 rdf:rest rdf:nil
84 Nbc98c6563c55493b977b08eb8332236f rdf:first sg:person.01244725741.43
85 rdf:rest N2cdfea5877a24e09982f0872289a328b
86 Nbe02a3aed08a4521b0a0b53e07004dfd schema:issueNumber 1
87 rdf:type schema:PublicationIssue
88 Nd00978cfb14943929407f6f22a63c485 schema:name readcube_id
89 schema:value de823dfd7789040fbe3163a684b0500f545ba9dcc5d85940e0e6c6adab0160a0
90 rdf:type schema:PropertyValue
91 Ne965d9af355a4500a68b397041f52b62 schema:name doi
92 schema:value 10.1186/s12885-018-4467-6
93 rdf:type schema:PropertyValue
94 Ne9c1dd0a1d4c41d5b9d116879f97577c rdf:first sg:person.014362730421.86
95 rdf:rest N4abb349852ce44e08a5478a5ef3046c1
96 Nff9569e6f28a40cd99d67e5de320897c schema:name pubmed_id
97 schema:value 29764404
98 rdf:type schema:PropertyValue
99 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
100 schema:name Medical and Health Sciences
101 rdf:type schema:DefinedTerm
102 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
103 schema:name Oncology and Carcinogenesis
104 rdf:type schema:DefinedTerm
105 sg:journal.1024632 schema:issn 1471-2407
106 schema:name BMC Cancer
107 rdf:type schema:Periodical
108 sg:person.01044677633.24 schema:affiliation https://www.grid.ac/institutes/grid.414816.e
109 schema:familyName Duran
110 schema:givenName Ignacio
111 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01044677633.24
112 rdf:type schema:Person
113 sg:person.01244725741.43 schema:affiliation https://www.grid.ac/institutes/grid.414816.e
114 schema:familyName Garrigos
115 schema:givenName Carmen
116 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01244725741.43
117 rdf:type schema:Person
118 sg:person.01265544650.31 schema:affiliation https://www.grid.ac/institutes/grid.7719.8
119 schema:familyName Apellaniz-Ruiz
120 schema:givenName María
121 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01265544650.31
122 rdf:type schema:Person
123 sg:person.01325400051.79 schema:affiliation https://www.grid.ac/institutes/grid.414816.e
124 schema:familyName de Álava
125 schema:givenName Enrique
126 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01325400051.79
127 rdf:type schema:Person
128 sg:person.014362730421.86 schema:affiliation https://www.grid.ac/institutes/grid.411109.c
129 schema:familyName Espinosa
130 schema:givenName Marta
131 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014362730421.86
132 rdf:type schema:Person
133 sg:person.015155427767.68 schema:affiliation https://www.grid.ac/institutes/grid.7719.8
134 schema:familyName Roldán-Romero
135 schema:givenName Juan Maria
136 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015155427767.68
137 rdf:type schema:Person
138 sg:person.0665541011.60 schema:affiliation https://www.grid.ac/institutes/grid.452372.5
139 schema:familyName Cascón
140 schema:givenName Alberto
141 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0665541011.60
142 rdf:type schema:Person
143 sg:person.0716606465.40 schema:affiliation https://www.grid.ac/institutes/grid.452372.5
144 schema:familyName Robledo
145 schema:givenName Mercedes
146 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0716606465.40
147 rdf:type schema:Person
148 sg:person.0755677367.02 schema:affiliation https://www.grid.ac/institutes/grid.452372.5
149 schema:familyName Rodriguez-Antona
150 schema:givenName Cristina
151 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755677367.02
152 rdf:type schema:Person
153 sg:pub.10.1007/s00261-014-0129-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047240020
154 https://doi.org/10.1007/s00261-014-0129-6
155 rdf:type schema:CreativeWork
156 sg:pub.10.1038/modpathol.2013.72 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007491127
157 https://doi.org/10.1038/modpathol.2013.72
158 rdf:type schema:CreativeWork
159 sg:pub.10.1186/1477-7819-10-181 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023300116
160 https://doi.org/10.1186/1477-7819-10-181
161 rdf:type schema:CreativeWork
162 https://doi.org/10.1002/gcc.2870130411 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038005025
163 rdf:type schema:CreativeWork
164 https://doi.org/10.1002/ijc.27800 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010380505
165 rdf:type schema:CreativeWork
166 https://doi.org/10.1002/path.2289 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010793228
167 rdf:type schema:CreativeWork
168 https://doi.org/10.1016/j.cell.2017.03.035 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084524353
169 rdf:type schema:CreativeWork
170 https://doi.org/10.1016/j.humpath.2007.01.028 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044406433
171 rdf:type schema:CreativeWork
172 https://doi.org/10.1016/s0140-6736(12)61767-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1047847005
173 rdf:type schema:CreativeWork
174 https://doi.org/10.1046/j.1469-1809.2003.00012.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1019494306
175 rdf:type schema:CreativeWork
176 https://doi.org/10.1056/nejmoa1403352 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050082768
177 rdf:type schema:CreativeWork
178 https://doi.org/10.1093/jjco/hyr035 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029699939
179 rdf:type schema:CreativeWork
180 https://doi.org/10.1097/pas.0b013e3181d90370 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010591966
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1097/pas.0b013e318206f2a9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030285373
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1111/iju.12095 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053259561
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1111/iju.12116 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025276639
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1111/j.1365-2559.2009.03420.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1018030987
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1111/j.1464-410x.2012.11618.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1035537607
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1126/science.1226344 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001422456
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1158/1078-0432.ccr-15-2631 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063225221
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1158/2159-8290.cd-13-0353 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010294909
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1159/000475142 schema:sameAs https://app.dimensions.ai/details/publication/pub.1082489447
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1200/jco.2009.25.2981 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027949240
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1200/jco.2009.26.3061 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021365418
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1371/journal.pgen.1006242 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017142251
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1371/journal.pone.0024919 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028361423
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1371/journal.pone.0158476 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042334411
209 rdf:type schema:CreativeWork
210 https://doi.org/10.2169/internalmedicine.48.2411 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035077670
211 rdf:type schema:CreativeWork
212 https://doi.org/10.3892/ol.2015.3846 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035118820
213 rdf:type schema:CreativeWork
214 https://doi.org/10.4081/rt.2013.e46 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039826284
215 rdf:type schema:CreativeWork
216 https://doi.org/10.5489/cuaj.2823 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072920617
217 rdf:type schema:CreativeWork
218 https://www.grid.ac/institutes/grid.411109.c schema:alternateName Hospital Universitario Virgen del Rocío
219 schema:name Medical Oncology Department, Hospital Virgen del Rocío, Servicio de Oncología Medica, Avenida Manuel Siurot s/n, 41013, Sevilla, Spain
220 rdf:type schema:Organization
221 https://www.grid.ac/institutes/grid.414816.e schema:alternateName Institute of Biomedicine of Seville
222 schema:name Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain
223 Medical Oncology Department, Hospital Virgen del Rocío, Servicio de Oncología Medica, Avenida Manuel Siurot s/n, 41013, Sevilla, Spain
224 Pathology Department, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla-CIBERONC, Sevilla, Spain
225 rdf:type schema:Organization
226 https://www.grid.ac/institutes/grid.452372.5 schema:alternateName Centre for Biomedical Network Research on Rare Diseases
227 schema:name Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain
228 Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029, Madrid, Spain
229 rdf:type schema:Organization
230 https://www.grid.ac/institutes/grid.7719.8 schema:alternateName Spanish National Cancer Research Centre
231 schema:name Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029, Madrid, Spain
232 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...